Infections of specific periodontal microbiota are associated with risk for age-related macular degeneration

项目总结 牙周微生物区系的特定组成与各种形式的牙周炎的风险有关。血清 抗体水平被认为是牙周微生物区系活动水平的替代标志，它代表了 微生物区系的蛋白质合成和炎症潜能。牙周微生物区系的慢性滴入 血流也会引起低级别的全身性炎症，这被认为会增加几个 口外疾病，如动脉粥样硬化、类风湿性关节炎、代谢紊乱和神经退行性疾病， 包括认知障碍和阿尔茨海默病。此外，我们最近的研究使用了来自第三季度的数据 国家健康和营养检查调查(NHANES III)表明，牙周的特定成分 微生物区系即使不会导致临床上显著的牙周炎，也可能对人类的风险产生重大影响。 疾病和死亡率，牙龈卟啉单胞菌在牙周生物失调中起关键作用 微生物区系。在这个提案中，我们将与相关学科的专家合作来测试我们的假设 特定牙周微生物群/P牙周炎的活动水平与老年性黄斑的发生有关 退行性变(AMD)。我们将首先使用偏最小二乘(PLS)回归来识别21种血清的特定模式 病例对照中牙周微生物区系中与AMD风险相关的免疫球蛋白G(IgG)水平 对具有代表性的美国人口样本的研究，NHANES III。最小二乘法是一种重要的统计方法 生物信息学，用于发现不能直接观察到但可以 而是从其他观察变量(即21个人的免疫球蛋白水平)推断出来的。因为我们的假设是新奇的，以前没有 本课题的研究已经完成，观察到的特定免疫球蛋白模式与AMD之间的关联可能会 尽管对令人困惑的变量进行了调整，但仍感到困惑。为了进一步验证关联，我们将使用补语 因子H(CFH)遗传多态作为孟德尔随机化研究的辅助变量。CFH基因 基因多态性是AMD的一个公认的危险因素。孟德尔随机化方法是一种新颖的方法 将遗传信息纳入传统流行病学方法和解决方案的流行病学研究设计 暴露-结果关系，没有影响传统流行病学有效性的许多典型偏差 接近了。当不可能进行随机试验时，孟德尔随机化方法特别有用。这 该项目将作为我们实现长期目标的第一步，即了解表型(如 血清学标记)和基因类型/菌株(微生物组)，以及人类基因组和 营养和其他已知的危险因素，影响眼睛健康。由于牙周炎是中国最常见的疾病之一 人类和AMD是老年人失明的主要原因，了解牙周与 微生物区系和AMD可能为AMD带来新的治疗和预防策略。

PROJECT SUMMARY Specific compositions of periodontal microbiota are associated with risk for the various forms of periodontitis. Serum antibody levels are considered as surrogate markers for the activity levels of periodontal microbiota, which represent the protein synthesis and inflammatory potential of the microbiota. The chronic trickling of periodontal microbiota into the bloodstream also elicits a low-grade systemic inflammation which has been suggested to increase the risk for several extra-oral diseases, such as atherosclerosis, rheumatoid arthritis, metabolic disorders, and neurodegenerative diseases, including cognitive impairment and Alzheimer's disease. Furthermore, our recent study using data from the Third National Health and Nutrition Examination Survey (NHANES III) indicated that specific compositions of periodontal microbiota, even without inducing clinically significant periodontitis, may have a significant impact on the risk for human disease and mortality, and that Porphyromonas gingivalis (P gingivalis) play a key role in the dysbiotic periodontal microbiota. In this proposal, we will collaborate with experts from related disciplines to test our hypothesis that the activity levels of specific periodontal microbiota/P gingivalis are associated with the occurrence of age-related macular degeneration (AMD). We will first use partial least squares (PLS) regression to identify specific patterns of 21 serum immunoglobulin G (IgG) levels for periodontal microbiota which are associated with the risk for AMD in a case-control study from a representative sample of the US population, the NHANES III. PLS is an important statistical method in bioinformatics and used to discover variables (i.e. specific patterns of IgG levels) that are not directly observed but are rather inferred from other observed variables (i.e. 21 individual IgG levels). Since our hypothesis is novel and no previous study in the topic has been done, it is possible that the observed associations between specific IgG patterns and AMD will be confounded in spite of adjusting for confounding variables. To further verify the associations, we will use complement factor H (CFH) genetic polymorphisms as an instrumental variable in our Mendelian randomization study. CFH genetic polymorphisms are a well-established risk factor for AMD. The Mendelian randomization approach is a novel epidemiologic study design that incorporates genetic information into traditional epidemiologic methods and addresses exposure-outcome relationships without many of the typical biases that impact the validity of traditional epidemiologic approaches. The Mendelian randomization approach is especially useful when a randomized trial is impossible. This project will serve as our first step toward our long-term objectives of understanding how the phenotypes (such as serological markers) and genotypes/strains (microbiome) of oral microbiota, together with the human genome and nutrition and other known risk factors, affect eye health. Since periodontitis is one of the most prevalent diseases in humans and AMD is the leading cause of blindness among elders, understanding the associations between periodontal microbiota and AMD may lead to new therapeutic and preventative strategies for AMD.